ObjectiveObesity has been identified as one of the most important risk factors for cognitive dysfunction. Physical exercise can ameliorate learning and memory deficits by reversing synaptic plasticity in the hippocampus and cortex in diseases such as Alzheimer’s disease. In this study, we aimed to determine whether 8 weeks of treadmill exercise could alleviate hippocampus-dependent memory impairment in high-fat diet-induced obese mice and investigate the potential mechanisms involved. MethodsA total of sixty 6-week-old male C57BL/6 mice, weighing between 20-30 g, were randomly assigned to 3 distinct groups, each consisting of 20 mice. The groups were designated as follows: control (CON), high-fat diet (HFD), and high-fat diet with exercise (HFD-Ex). Prior to the initiation of the treadmill exercise protocol, the HFD and HFD-Ex groups were fed a high-fat diet (60% fat by kcal) for 20 weeks. The mice in the HFD-Ex group underwent treadmill exercise at a speed of 8 m/min for the first 10 min, followed by 12 m/min for the subsequent 50 min, totally 60 min of exercise at a 0° slope, 5 d per week, for 8 weeks. We employed Y-maze and novel object recognition tests to assess hippocampus-dependent memory and utilized immunofluorescence, Western blot, Golgi staining, and ELISA to analyze axon length, dendritic complexity, number of spines, the expression of c-fos, doublecortin (DCX), postsynaptic density-95 (PSD95), synaptophysin (Syn), interleukin-1β (IL-1β), and the number of major histocompatibility complex II (MHC-II) positive cells. ResultsMice with HFD-induced obesity exhibit hippocampus-dependent memory impairment, and treadmill exercise can prevent memory decline in these mice. The expression of DCX was significantly decreased in the HFD-induced obese mice compared to the control group (P<0.001). Treadmill exercise increased the expression of c-fos (P<0.001) and DCX (P=0.001) in the hippocampus of the HFD-induced obese mice. The axon length (P<0.001), dendritic complexity (P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P<0.001) in the hippocampus were significantly decreased in the HFD-induced obese mice compared to the control group. Treadmill exercise increased the axon length (P=0.002), dendritic complexity(P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P=0.001) of the hippocampus in the HFD-induced obese mice. Our study found a significant increase in MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of HFD-induced obese mice compared to the control group. Treadmill exercise was found to reduce the number of MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of obese mice induced by a HFD. ConclusionTreadmill exercise led to enhanced neurogenesis and neuroplasticity by increasing the axon length, dendritic complexity, dendritic spine numbers, and the expression of PSD95 and DCX, decreasing the number of MHC-II positive cells and neuroinflammation in HFD-induced obese mice. Therefore, we speculate that exercise may serve as a non-pharmacologic method that protects against HFD-induced hippocampus-dependent memory dysfunction by enhancing neuroplasticity and neurogenesis in the hippocampus of obese mice.

Objective To analyze the distribution characteristics of the single nucleotide polymorphism (SNP) site rs76206423 in the promoter region of the interleukin-2 receptor (IL-2R) β gene among Han males in a high radiation background area (HBRA) in Yangjiang City. Methods A total of 48 male participants from Tangkou Town, Yangxi County, Yangjiang City (HBRA group), and 51 male participants from Hengpo Town, Enping City (control group) were selected as the research subjects using the random number table method. Peripheral venous blood samples of participants from both groups were collected, and genomic DNA was extracted. The genotyping and allele frequency distribution of the rs76206423 (A/G) site in the IL-2R β promoter region was detected among the participants in both groups using the SNP detection method. The difference of allele frequencies between population in HBRA group and five area of East Asia, South Asia, Africa, Europe, and the Americas published in the Human Genome Project database from National Center for Biotechnology Information were analyzed. Results The allele frequencies of rs76206423 of population in both groups conformed to Hardy-Weinberg equilibrium (P>0.05). In the HBRA group, the AA genotype was predominant (64.6%), while the AG genotype was the most common in the control group (51.0%), with a significant difference (P<0.05). Population in both groups showed a predominance of the variant allele A (78.1% and 72.5%, respectively), with no significant difference (P>0.05). The frequency of the G allele of rs76206423 in the population in HBRA group was higher than those in South Asian, African, European, and American populations (all P<0.01), but showed no significant difference compared with East Asian populations (P>0.05). Conclusion In the Han male population from the HBRA in Yangjiang City, the rs76206423 site in the IL-2R β gene promoter region is predominantly composed of the wild-type A allele and AA genotype, indicating genetic stability and a relatively high degree of variation at this locus.

Objective To analyze the differences of clinical features of acute gout flare and postoperative infection under arthroscopy of knee gouty arthritis patients to offer guiding opinions of clinical diagnosis and treatment.Methods Between Jan-uary 2017 and December 2022,235 patients with gouty knee osteoarthritis were admitted,and underwent arthroscopic debride-ment combined with synovectomy.Among them,35 cases had fever with a temperature higher than 38 ℃ postoperatively while acute inflammatory appears under redness,swelling,heat and pain of the operated joints.There were 29 males and 6 females,with an average age of(41.48±13.90)years old.Among them 23 patients were diagnosed with acute gout attack,and recovered well after being given colchicine and prednisolone;12 patients were diagnosed with postoperative joint infection,and were cured after being given anti-infective treatments and cleaning and rinsing of the joint cavity.The two groups of patients were compared and analyzed in terms of preoperative general data,surgical conditions,hematology,joint fluid,limb function and other clinical characteristics.Results There were no significant difference in the preoperative general data between two groups.The onset of fever in the postoperative acute gout flare group occurred mostly within 48 hours,significantly earlier than that in the postoperative infection group(P=0.037).The visual analogue scale score was significantly higher in the acute gout flare group(5.32±1.38)score than in the postoperative infection group(2.45±0.68)score(P=0.000),while 14 patients with acute gout flare were accompanied by severe pain in other joints.Hematologically,indicators such as white blood cell counts and ra-tios were significantly higher in both groups.In terms of inflammatory indicators,IL-6,erythrocyte sedimentation rate,procal-citonin and other inflammatory indicators were significantly elevated in both groups,but there was no statistical difference be-tween two groups.The C-reactive protein level in the postoperative infection group(220.97±1 16.30)mg·L-1 was higher than that in the postoperative acute gout attack group(120.67±82.45)mg·L-1(P=0.006).Blood uric acid(316.55±112.84)μmol·L-1 was higher in the acute postoperative gout flare group than in the postoperative infection group(159.14±126.92)μmol·L-1(P=0.001).In the joint fluid examination of the postoperative infection group,the glucose metabolism indicator was signifi-cantly lower than that of the acute gout flare group,and five of them had positive bacterial cultures Conclusion The symptoms of acute gout flare could be mistaken as postoperative infection due to their similarity,therefore requires careful differentiation.Differential diagnosis should be based on a combination of clinical signs,hematology and joint fluid findings,and targeted treatment should be given to avoid serious complications.

Objective To explore the efficacy of vaginal lesion resection combined with uterine wall repair in the treatment of cesarean scar pregnancy(CSP)after cesarean section.Methods A total of 122 patients with CSP admitted to our hospital were selected and randomly divided into the control group(61 cases)and the observation group(61 cases).Patients in the control group were treated with uterine artery chemoembolization(UACE)combined with ultrasound-guided curettage,while patients in the observation group were treated with vaginal lesion resection combined with uterine wall repair.The perioperative index,serum beta-human chorionic gonadotropin(β-hCG)levels before surgery and 3 days,5 days,and 7 days after surgery,clinical efficacy,and complications of patients between the groups were compared.Results The operation time of patients in the observation group was significantly longer than that in the control group(P<0.05),and the amount of intraoperative blood loss,hospitalization cost,vaginal bleeding time,time to menstruation recovery,mass disappearance time,β-hCG normalizing time,and hospitalization time of patients in the observation group were significantly less/shorter than those in the control group(P<0.05).The serum β-hCG levels of patients 3 days,5 days and 7 days after surgery in both groups were lower compared with those before surgery,and the observation group was lower than the control group,with statistically significant differences(P<0.05).The total effective rate in the observation group was 96.72%,significantly higher than that of 85.25%in the control group(P<0.05).The incidence of vaginal bleeding and surrounding tissue injury in the observation group was significantly lower than that in the control group(P<0.05).Conclusion The combination of vaginal lesion resection and uterine wall repair for the treatment of CSP can reduce the amount of intraoperative blood loss,reduce the serum β-hCG levels and the incidence of complications,improve clinical treatment efficacy,and promote recovery of patients.

Diabetes mellitus is a metabolic disease with high incidence and many complications,among which type 2 diabetes mellitus(T2DM)accounts for a large proportion.Current studies have shown that T2DM is accompanied by damage of liver,kidney,and other organs and its complications seriously en-danger human health.Ferroptosis generates many Reactive Oxygen Species(ROS)through the Fenton reaction,and the accumulation of ROS activates Hypoxia Inducible Factor-1(HIF-1α).As a result,the level of vascular endothelial growth factor(VEGF)is increased.Ferrostatin-1(Fer-1),a ferroptosis in-hibitor,has strong antioxidant capacity.Therefore,based on the hypoxia-inducible factor-1α/vascular endothelial growth factor(HIF-1α/VEGF)signaling pathway,we explored the therapeutic effect of Fer-1 on the liver and kidney tissues of diabetic mice.db/db mice(21～22 weeks old)were used as the model of diabetes mellitus.Ferroptosis inhibitor Fer-1 was used as the intervention drug.db/m mice served as the blank control group,and body weight and blood glucose were measured for 4 weeks.Food intake and water intake were recorded in each group.The levels of Alanine aminotransferase(ALT)and Aspartate aminotransferase(AST)in the serum were measured.ROS and Glutathione(GSH)activity in liver and kidney tissues and urinary protein content were measured.Liver and kidney tissue sections were stained with Hematoxylin-Eosin(HE),and the pathological morphology was observed under a light microscope.The protein levels of HIF-1α,VEGF,and glutathione peroxidase 4(GPX4)in liver and kidney tissues were detected by Western blot.In db/db mice,Fer-1(1 mg·kg-1,ig)could significantly reduce the a-mount of food and water intake,the levels of ALT and AST in serum,the ROS production in liver and kidney tissues,and the level of urine protein,but significantly increase the activity of GSH,thus improve the pathological conditions of liver and kidney.Fer-1 also significantly inhibited HIF-1α and VEGF pro-tein indexes and increased GPX4 protein levels in liver and kidney tissues.Although Fer-1 can not change the body weight and reduce blood glucose in diabetic mice,it can play a therapeutic role in the liver and kidney tissues of diabetic mice in the middle and late stages,and its mechanism may be related to HIF-1α/VEGF and GPX4.

Objective:To investigate the clinical significance of bone metabolic indexes for disease assessment and curative effect monitoring in multiple myeloma(MM)bone disease(MBD)patients with different blood separation results.Methods:A total of 134 newly diagnosed MM patients treated in Cangzhou Hospital of Integrated TCM-WM-Hebei were enrolled and divided into control group[119 cases,serum,colloid and red blood cell(RBC)from top to bottom of sample]and abnormal group(15 cases,serum,mixed layer of RBC and serum,colloid and RBC from top to bottom of sample)according to the results of blood separation.According to the imaging findings,MBD was classified into grade 0-4,grade 0-2 was mild,and grade 3-4 was severe.The MBD grade of patients in the two groups was analyzed.The curative effect of MBD patients after chemotherapy and the changes of blood separation results and bone metabolic indexes before and after treatment were evaluated.The correlation between β 2-microglobulin(MG)and bone metabolic indexes was analyzed by Pearson correlation analysis.Results:In the control group,there were 69 cases of grade 0-2 and 50 cases of grade 3-4,while in the abnormal group,there were 5 cases of grade 0-2 and 10 cases of grade 3-4,the difference was statistically significant(P＜0.05).The serum β 2-MG,β-CTX levels in abnormal group were both significantly higher than those in control group,while the levels of P1NP and osteocalcin(OC)were significantly lower(all P＜0.001).In the control group,there were 95 patients with ≥ partial response(PR)and the blood separation results were not changed,while 24 patients with＜PR and 5 of them had abnormal blood separation results.In the abnormal group,9 patients with efficacy≥PR showed normal blood separation results,while 6 patients with efficacy＜PR and 5 of them still remained abnormal blood separation results.Compared with before treatment,β-CTX and β 2-MG of patients with efficacy ≥ PR were significantly decreased but P1NP and OC increased in the control group(all P＜0.00 1),which was the same as abnoraml group(both P＜0.001,P＜0.01).There were no significant changes in the levels of all indexes in the two groups of patients with efficacy＜PR(P＞0.05).Compared with before treatment,the levels of β-CTX and β 2-MG in the control group with unchanged blood separation results were significantly decreased(both P＜0.00l),while the levels of P1NP and OC were significantly increased(P＜0.01,P＜0.001),and the level of each index in the patients transformed to abnormal blood separation result after treatment did not significantly change(P＞0.05);the levels of β-CTX and β 2-MG in the abnormal group transformed to normal blood separation result were significantly decreased(both P＜0.01),while the levels of P1NP and OC were significantly increased(P＜0.001,P＜0.01),and the level of each index in patients with unchanged blood separation results did not significantly change(P＞0.05).Pearson correlation analysis showed that serumβ 2-MG was positively correlated with β-CTX(r=0.709,P＜0.001),and negatively correlated with P1NP and OC(r=-0.410,r=-0.412,both P＜0.001).Conclusion:MBD patients with abnormal blood separation results have higher bone disease grade and poor prognosis,which is closely related to the significant increase of bone resorption index β-CTX level and decrease of bone formation index P1NP and OC levels,leading to more serious bone metabolic homeostasis disorder.The results of blood separation combined with the changes of bone metabolic indexes can be used as one of the comprehensive predictors of disease condition,efficacy monitoring and prognosis evaluation of MBD patients.

Objective:To detect the pharmacokinetic(PK)parameters of coagulation factor Ⅷ(FⅧ)in adult patients with severe hemophilia A,identify the potential factors influencing FⅧ PK,and optimize the use of FⅧ in individual prophylaxis regimens.Methods:PK characteristics of FⅧ were studied in a total of 23 severe hemophilia A adults.The correlation of patients'characteristics including age,von Willebrand factor antigen(vWF:Ag),blood group,weight,body mass index(BMI)and FⅧ genotype,with FⅧ PK were evaluated.Individual prophylaxis regimens were given based on FⅧ PK parameters.Results:The mean terminal half-life(t1/2)of FⅧ was 20.6±9.3 h,ranged from 11.47 h to 30.12 h.The age(r=0.580)and vWF:Ag(r=0.814)were significantly positively correlated with t1/2 of FⅧ.The mean area under the plasma concentration curve(AUC)of FⅧ was 913±399(328-1 878)IU h/dl,and the AUC of FⅧ was positively correlated with age(r=0.557)and vWF:Ag(r=0.784).The mean residence time(MRT)of FⅧ was 24.7±12.4(13.2-62.2)h,and the MRT of FⅧ was positively correlated with age(r=0.664)and vWF:Ag(r=0.868).The mean in vivo recovery(IVR)of FⅧ was 2.59±0.888(1.5-4.29)IU/dl per IU/kg,the mean clearance(CL)of FⅧ was 3±1.58(0.97-7.18)ml/(kg·h),and there was no significant correlation of IVR and CL with age and vWF:Ag.According to the individual PK parameters,ultra low-dose,low-dose and moderate-dose FⅧ were applied to 15,6,2 adults patients with severe hemophilia A for prophylaxis,respectively.Conclusion:There are significant individual differences in the FⅧ half-life of adult patients with severe hemophilia A.The older the patient,the higher the vWF:Ag level,and the longer the FⅧ half-life.Individual administration is required based on the FⅧ PK parameters to optimize prophylaxis treatment.

Objective:This study aims to develop a validated instrument for assessing the degree of integration perceived by patients in the services provided by general practitioner(GP)teams,and to evaluate the current state of integrated medical-prevention services.Methods:The survey tool was initially created through a review of existing literature and semi-structured interviews.It was subsequently refined and enhanced following consultations with experts.The utility of the instrument was confirmed through empirical research,which also facilitated an analysis of the status quo regarding the integration of medical and prevention services.Results:The devised instrument encompasses 18 items distributed across six dimensions:service comprehensiveness,service continuity,depth of service,continuity of relationship,patient-centricity,and service coordination.The cumulative score reflecting patients'perception of the integration level in GP teams'medical-prevention services was 54.30±12.45.Conclusion:The survey instrument developed in this research is characterized by its rationality,novelty,and practical relevance.It offers a patient-centered perspective for assessing the quality of integrated medical and prevention services for primary chronic diseases.While the overall perception of integration among patients is positive,there is a notable deficiency in the depth of services provided.There is a need for optimization of the service process,clarification of the service path,refinement of service management,and development of an integrated incentive mechanism for medical and preventive care,aiming for a deeper integration between medical services and preventive care.

Objective:To investigate the predictive value of plasma exosome count for the prognosis of patients with sepsis.Methods:A prospective observational study was conducted. The patients with sepsis admitted to intensive care unit (ICU) of Zhejiang Hospital from November 2020 to December 2021 were enrolled as the study subjects. On the 1st day of admission to the ICU, the patient's gender, age, underlying disease, infection site, mean arterial pressure (MAP) and severity scores were recorded, and venous blood was taken for detecting the blood routine, blood biochemistry, and procalcitonin (PCT), and arterial blood was taken for blood gas analysis, simultaneously, the patient's noradrenaline (NA) dosage was recorded. On the 1st, 3rd, 5th, and 7th day of ICU admission, plasma exosomes were extracted, and the number of exosomes was detected by nanoparticle tracking analyzer. The endpoint of observation was the death of the patient 28 days after admission to the ICU. The differences in baseline data and plasma exosome counts of patients with different 28-day prognosis were analyzed and compared. The Spearman correlation method was used to analyze the correlation between plasma exosome counts and other clinical indicators. Binary multivariate Logistic regression analysis was used to screen the 28-day death risk factors of septic patients. The receiver operator characteristic curve (ROC curve) was plotted to analyze the predictive value of each index on the 28-day death of septic patients. The Kaplan-Meier method was used to analyze the 28-day survival curve.Results:A total of 26 patients with sepsis were enrolled, of whom 21 survived and 5 died on the 28th day. Compared with the survival group, the patients in the death group had lower MAP, higher sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, white blood cell count (WBC), cardiac troponin I (cTnI), and worse oxygenation. The plasma exosome count on the 1st day of ICU admission in the death group was significantly higher than that in the survival group (×10 15/L: 16.96±9.11 vs. 5.20±2.42, P < 0.05). Subsequently, the plasma exosome counts in both groups continued to decrease, and there was no statistically significant difference between the two groups. Spearman correlation analysis showed that the plasma exosome count on the 1st day of ICU admission in septic patients was significantly positively correlated with SOFA score, APACHEⅡ score, blood lactic acid (Lac), alanine aminotransferase (ALT) and NA dosage ( r values were 0.572, 0.585, 0.463, 0.411, 0.696, all P < 0.05), and it significantly negatively correlated with MAP and oxygenation index (PaO 2/FiO 2; r values were -0.392 and -0.496, both P < 0.05). Multivariate Logistic regression analysis showed that plasma exosome count on the 1st day of ICU admission was an independent risk factor for 28-day death in septic patients [odds ratio ( OR) = 1.385, 95% confidence interval (95% CI) was 1.075-1.785, P = 0.012]. ROC curve analysis showed that the area under the ROC curve (AUC) of plasma exosome count on the 1st day of ICU admission for predicting 28-day death in septic patients was 0.800 (95% CI was 0.449-1.000); when the optimal cut-off value was 14.50×10 15/L, the sensitivity was 80.0% and the specificity was 100%. According to the optimal cut-off value of 1-day plasma exosome count, the patients were divided into two groups for Kaplan-Meier survival curve analysis, and the results showed that the cumulative survival rate of patients with plasma exosome count < 14.50×10 15/L was significantly higher than that of patients with plasma exosome count ≥ 14.50×10 15/L (Log-Rank test: χ2 = 19.100, P < 0.001). Conclusion:The plasma exosome count of septic patients is significantly increased on the 1st day of admission to the ICU, which is related to the severity, and can predict the risk of death at 28 days.

Objective:To study the expression of the Homeobox C6(HOXC6)gene in the homeobox family in PCa,its effect on the biological behavior of PCa cells and its action mechanism.Methods:Based on the studies of HOXC6 retrieved from the data-base of Gene Expression Profiling Interactive Analysis(GEPIA),we analyzed the expression of HOXC6 in PCa and the relationship of its expression level with the survival prognosis of the patients.We detected the expression of the HOXC6 protein in PCa tissues and cells by Western blot,stably interfered with the expression of the HOXC6 gene in human PCa DU145 and PC-3 cells and normal prosta-tic epithelial RWPE-1 cells using the siRNA plasmid,and determined the effects of HOXC6 on the proliferation,migration and inva-siveness of PCa cells by CCK8,plate cloning and scratch healing and Transwell invasion assays.Using the GEPIA database,we ana-lyzed the correlation of the Wnt tumor inhibitory factor-secreted frizzled-related protein 1(SFRP1)gene with HOXC6,and detected the expressions of HOXC6,SFRP1,Wnt and β-catenin in PC-3 cells after siRNA-HOXC6 transfection by Western blot.Results:The expression of HOXC6 was dramatically higher in the PCa than in the normal prostate tissue(P<0.01),and in the PCa cells than in the normal prostatic epithelial cells(P<0.01).Bioinformatics analysis indicated a lower survival rate of the PCa patients with a high than those with a low HOXC6 expression(P=0.011).The relative expression of the HOXC6 protein,absorbance value,number of clones formed and number of invaded cells were significantly lower in the siRNA group than in the negative controls(P<0.05).Ac-cording to the GEPIA database,highly expressed SFRP1 was associated with a good prognosis of PCa,and the protein expressions of Wnt and β-catenin were markedly increased while that of SFRP1 decreased in the PCa PC-3 cell line(P<0.05).The expressions of the Wnt and β-catenin proteins were decreased and that of SFRP1 increased significantly in the siRNA-HOXC6 transfection group com-pared with those in the siRNA negative control and PCa PC-3 groups(P<0.05).Conclusion:HOXC6 is highly expressed in PCa tissues and related to the proliferation,migration and invasiveness of PCa cells.HOXC6 promotes the growth of DU145 and PC-3 cells in PCa by inhibiting the SFRP1/Wnt/β-catenin signaling pathway,and may be a potential target for clinical treatment of PCa.